Dichloromethane → Tadalafil Impurity 11

HRID 540995Notes

Reaction equation

HRID 540995 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:17])[C@@H:5]([CH2:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1)[NH2:6].[CH:18]1[C:23]([CH:24]=O)=[CH:22][C:21]2[O:26][CH2:27][O:28][C:20]=2[CH:19]=1.[Cl:29]CCl>S1(CCCC1)(=O)=O>[ClH:29].[CH3:2][O:3][C:4]([C@@H:5]1[CH2:7][C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]=2[C@H:24]([C:23]2[CH:18]=[CH:19][C:20]3[O:28][CH2:27][O:26][C:21]=3[CH:22]=2)[NH:6]1)=[O:17]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 8438PiperonalHCID 11448200methyl (2R)-2-amino-3-(1H-indol-3-yl)propanoate hydrochloride

Product 1

HCID 44250481Tadalafil Impurity 11

Reagents, catalysts & solvents 1

HCID 31347SulfolaneSolvent

Procedure

D-tryptophan methyl ester hydrochloride of Step 1 (100 g) and piperonal (65 g) were suspended in sulfolane (500 mL) at 25° C. to 30° C. The reaction mixture was heated to 80° C. to 85° C., stirred for 14 hours, and then cooled to 25° C. to 30° C. To the cooled mixture, dichloromethane (500 mL) was added and the resultant mixture was stirred continuously for 1 hour. The solid obtained was filtered, washed with dichloromethane (500 mL), and dried in air at 40° C. to 45° C. to afford cis 1-benzo[1,3]dioxol-5-yl-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylic acid methyl ester hydrochloride.

Workup

  1. temperatureThe reaction mixture was heated to 80° C. to 85° C.
  2. temperaturecooled to 25° C. to 30° C
  3. customThe solid obtained
  4. filtrationwas filtered
  5. washwashed with dichloromethane (500 mL)
  6. customdried in air at 40° C. to 45° C.

Sources & evidence

ORD record
ord-8b682bd17854417093b72289a6c1f573
Source dataset
uspto-grants-2014_10
Patent number
US08871932B2

Reaction notes

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